Featured Research

from universities, journals, and other organizations

Common molecular defect offers treatment hope for group of rare disorders

Date:

April 1, 2014

Source:

Duke Medicine

Summary:

Researchers studying tiny, antennae-like structures called cilia have found a potential way to ease some of the physical damage of numerous genetic disorders that result when these essential cellular components are defective. Different genetic defects cause dysfunction of the cilia, which often act as sensory organs that receive signals from other cells. Individually, disorders involving cilia are rare, but collectively the more than 100 diseases in the category known as ciliopathies affect as many as one in 1,000 people.

Share This

Duke Medicine researchers studying tiny, antennae-like structures called cilia have found a potential way to ease some of the physical damage of numerous genetic disorders that result when these essential cellular components are defective.

Related Articles

Different genetic defects cause dysfunction of the cilia, which often act as sensory organs that receive signals from other cells. Individually, disorders involving cilia are rare, but collectively the more than 100 diseases in the category known as ciliopathies affect as many as one in 1,000 people. Ciliopathies are characterized by cognitive impairment, blindness, deafness, kidney and heart disease, infertility, obesity and diabetes.

Recent research has added key insights into the overall role and function of cilia in cells and what occurs when the organelle is defective.

"Cilia are required for regulation of a whole host of signaling pathways for cellular development," said Nicholas Katsanis, PhD, professor of cell biology and director of the Center for Human Disease Modeling at Duke. "They are not the only signaling regulators, but they are critical. It's been important for us to understand how they do this."

In the current study, published April 1, 2014, in the Journal of Clinical Investigation, Katsanis and colleagues describe a common mechanism that appears to account for how dysfunctional cilia cause so many different problems in cellular signaling pathways.

Using both cells and animal models, they focused on the ubiquitin-proteasome system, the cell's machinery tasked with regulating the cellular environment by breaking down proteins that are either damaged or in need of removal.

"Imagine regular housekeeping" Katsanis said. "Taking out waste is part and parcel to the process, but not if you end up throwing away your valuables."

The researchers also set out to test whether they could somehow bolster the function of the proteasome to see if this would have a therapeutic effect. When non-defective genes were introduced in zebrafish, the animals showed physical improvements indicative of corrections in multiple signaling pathways, Katsanis said.

More significantly, similar improvements occurred in the animals by administering common compounds, including mevalonic acid and the nutritional supplement sulforaphane, an antioxidant found in broccoli and other cruciferous vegetables. Both are known to improve proteasomal activity.

"While the animals were not as good as normal controls, they were much better -- we saw clear physical improvement with each of the compounds," Katsanis said. "This now gives us a hypothesis that explains at least in part why, for whatever reason ciliopathy is caused, it can result in different signaling pathways going awry, and a potential avenue for therapies."

Katsanis said additional research should focus on the proteasome system, and other potential therapeutic targets that could improve the proteasome.

"Understanding cilia dysfunction is important, because its association with so many disorders pose a significant societal and medical burden. And we look forward to seeing wither the insights we have learned in these studies are applicable to other diseases," Katsanis said, adding that more work will be required to follow up this lead.

"As exciting as these findings are, we need to act cautiously and responsibly before we jump into clinical trials in humans," he said. "Nonetheless, there is now a clear path toward that goal."

Story Source:

The above story is based on materials provided by Duke Medicine. Note: Materials may be edited for content and length.

More From ScienceDaily

More Plants & Animals News

Featured Research

Mar. 31, 2015 — Researchers have recorded the first direct observations of the micro-scale mechanisms behind the ability of skin to resist tearing. The results could be applied to the improvement of artificial skin, ... full story

Mar. 31, 2015 — Soil organic matter, long thought to be a semi-permanent storehouse for ancient carbon, may be much more vulnerable to climate change than previously thought. Scientists have found that the common ... full story

Mar. 31, 2015 — Using the assessment tool ForWarn, US Forest Service researchers can monitor the growth and development of vegetation that signals winter's end and the awakening of a new growing season. Now these ... full story

Mar. 31, 2015 — Until now electric fences and trenches have proved to be the most effective way of protecting farms and villages from night time raids by hungry elephants. But researchers think they may have come up ... full story

Mar. 31, 2015 — The endangered desert pupfish has made itself at home in the harsh, hot environment of Death Valley hot springs by using a surprising evolutionary adaptation: They can go for up to five hours without ... full story

Mar. 31, 2015 — Researchers have detected a human fingerprint deep in the Borneo rainforest in Southeast Asia. Cold winds blowing from the north carry industrial pollutants from East Asia to the equator, with ... full story

Mar. 31, 2015 — A team of engineers and biologists reports new progress in using computer modeling and 3D shape analysis to understand how the unique grasping tails of seahorses evolved. These prehensile tails ... full story

Mar. 31, 2015 — As the five-year anniversary of the explosion of the Deepwater Horizon oil rig approaches, a new report looks at how twenty species of wildlife are faring in the aftermath of the ... full story

Mar. 31, 2015 — Scientists have uncovered the earliest fossilized evidence of an insect caring for its young. The findings push back the earliest direct evidence of insect brood care by more than 50 million years, ... full story

Giant Amphibian Fossils Found in Portugal

Reuters - Light News Video Online (Mar. 31, 2015) — Scientists discover a new species of giant amphibian that was one of the largest predators on earth about 220 million year ago. Tara Cleary reports.
Video provided by Reuters

Bionic Ants Could Be Tomorrow's Factory Workers

Reuters - Innovations Video Online (Mar. 30, 2015) — Industrious 3D printed bionic ants working together could toil in the factories of the future, says German technology company Festo. The robotic insects cooperate and coordinate their actions and movements to achieve a common aim. Amy Pollock reports.
Video provided by Reuters

Related Stories

Dec. 18, 2014 — It is difficult to diagnose, study and treat cioliopathies, because it is difficult to examine cilia in molecular detail. Now researchers report that they have captured the highest-resolution images ... full story

Sep. 9, 2014 — Another mystery of the human body has been solved by scientists who have identified how a molecular motor essential for human development works. They have also pinpointed why mutations in genes ... full story

July 1, 2014 — The functions of a gene responsible for anchoring cilia – sensory hair-like extensions present on almost every cell of the body -- have been described by researchers. They show in a mouse model ... full story

Apr. 24, 2012 — Primary cilia are hair-like structures which protrude from almost all mammalian cells. They are thought to be sensory and involved in sampling the cell’s environment. New research shows that cilia ... full story

Apr. 4, 2011 — Researchers have described a previously unknown role for the cilia protein IFT88 in mitosis, the process by which a dividing cell separates its chromosomes containing the cell's DNA into two ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.